In the process of drug development, in vitro (=“on glass”) microscopy performed in cultured cells or tissue slices is usually followed by (and iteratively combined with) in vivo studies that rely on imaging technologies such as PET, MRI or bioluminescence imaging of living animals
(= in vivo).
Unfortunately, the distinct benefits offered by these two techniques (in vitro microscopy and in vivo imaging) cannot be combined synergistically to boost the less-than-optimal predictive power of preclinical disease models and to lower the soaring attrition rates.
Thus, conventional in vitro microscopy offers excellent resolution (tens to hundreds of nanometers), but the relevance of results obtained on dissociated cells or fixed tissue sections is undoubtedly low, since the cells are either kept alive in a highly unnatural environment of a Petri dish or are, bluntly speaking, killed by fixation and sectioning.
On the other hand, in vivo imaging technologies conventionally employed in drug discovery and development, offer highly relevant images with quite poor resolution (hundreds of micrometer to millimeter scale).
At present, only in vivo two-photon microscopy combines the crucial advantages of both conventional techniques: it allows researchers to obtain high relevance images (within a live animal) with high resolution (nanometer scale), as illustrated in the diagram below:
